Method for manufacturing endo-osseous implants or medical prosthesis by ionic implantation technique

ABSTRACT

The method comprises the ion implantation of controlled quantities of elements such as CO, C or O in endo-osseous implants or prostheses manufactured in metals, metallic alloys or biocompatible compound materials. This surface treatment originates some modifications in the characteristics of the surface of the endo-osseous implants or prostheses which increases significantly their degree of osseointegration.

FIELD OF THE INVENTION

[0001] This invention is related, in general, with surface treatments ofimplants and medical prostheses to improve their osseointegrationproperties, in particular, it refers to a method for the production ofendo-osseous implants or prostheses manufactured in a base material andtreated superficially by means of ion implantation with enhancedosseointegration properties.

BACKGROUND OF THE INVENTION

[0002] The requirement for prosthetic treatments of long duration(implants or knee, hip, maxillofacial, cranial, etc. prostheses), isincreasingly usual in daily clinical practice, and involves the use, innumerous cases, of metallic materials (subcutaneous or osseous implants)mainly in patients subjected to major traumatic surgery, maxillofacialsurgery, osteoporotic and osteoproliferative patients. The employment ofthese systems of prosthetic substitution is accompanied by a notinsignificant implant failure rate, which in some cases surpasses 30%,and at times makes recourse to this technique an impossibility.

[0003] The most frequent complications encountered, described in themedical literature, are the infectious type (infection of the implant,bacteremia, sepsis, and others less frequent, like gangrene, etc.), theinflammatory type (reaction to a foreign body, local inflammation, totalrejection), those of tissue integration (gingivitis, sinovialmetallosis, osteoresorption) and those arising from their handling anduse (rupture of the bone, failure of the metal-tissue interface).

[0004] The biocompatible metals constitute the most important anddiverse group of materials used in biomedical applications because theyoffer appropriate properties of biocompatibility and chemical inertiawhich make them suitable for contact with biological fluids and tissues.Also, they have the characteristic that they can be manufactured in agreat variety of ways.

[0005] However, the evolution observed in recent years regarding thetypes of alloys employed has not reduced the number of complications asmuch as would have been expected and the experimental procedures used toimprove their biocompatibility have been limited to more permeabledesigns or surface impregnations, more or less intense, with moleculeshaving biological activity (antibiotics, antiseptics, antiaggregants,etc.).

[0006] The requirement remains to develop medical materials whoseemployment permits avoidance of the entirety or part of theaforementioned complications.

[0007] In that concerning the problem of osseointegration of theprostheses or implants, a method of approaching the problem couldconsist in applying a surface treatment thereon which confers upon themthe appropriate characteristics.

[0008] This is the case of ion implantation, a treatment which does notmodify the structural properties or the dimensional tolerances of thetreated prostheses or implants (see FIG. 1) but which, however, canmodify their surface properties by means of the introduction of a seriesof selected elements on the surface, modifying the properties thereof inthe desired sense.

[0009] Use has been made of different techniques of ion implantation formany years in different fields of application with the object ofmodifying the surface properties of the components. It is used, forexample, in electronics for modification of the electrical properties ofsemiconductors. It is also applied in the metal mechanics industry forthe improvement of properties of resistance to abrasion and corrosion,in cases such as moulds and injection mouthpieces, machining and cuttingtools, gauges, etc.

[0010] Ion implantation has also been used on biomaterials. This is thecase, for example, of the implantation of germicidal elements in medicalequipment described in U.S. Pat. No. 5,492,763, or the implantation inimplants of cobalt-chromium alloys with the object of increasing surfacehardness and reducing friction as described in European patentapplication EP 526 581. The problem of osseointegration has also beenbroached from the ion implantation technique in order to produce asurface coated with hydroxyapatite, a coating which has also beenapplied by other processes. Such is the case of the method for theproduction of surgical implantations coated with synthetic bonedescribed in Spanish patent ES 2.006.658 which employs high energystreams of xenon to coat the implants with hydroxyapatite by thesputtering or cathodic spraying technique. German patent application DE19830530 describes the production of titanium surfaces coated withcalcium phosphate by ion implantation. In this last case, use is made ofphosphorus and calcium implantation followed by a heat treatment.

[0011] Notwithstanding the existence of previous applications of ionimplantation in implants and medical prostheses, the ion implantationmethods employed provide implants and prostheses with insufficientosseointegration properties and/or with a risk of lixiviation of theions to the physiologic medium in contact with the inadequate implantsand prostheses, and/or with not completely satisfactory tribologicalproperties.

SUMMARY OF THE INVENTION

[0012] The invention confronts the problem of providing endo-osseousimplants and prostheses, superficially treated by ion implantation, withcharacteristics of enhanced osseointegration.

[0013] The solution provided by this invention comprises the developmentof a method for the production of said implants and medical prosthesesdesigned to overcome the problems of osseointegration thereof in theosseous structures and is based in that the ion implantation ofcontrolled quantities of certain elements and/or compounds in saidimplants or prostheses, under certain conditions, allows endo-osseousimplants and/or medical prostheses to be obtained with an enhanceddegree of osseointegration thereof, and/or with a reduced degree oflixiviation of ions to the physiological medium, and/or with enhancedtribological properties.

BRIEF DESCRIPTION OF THE FIGURES

[0014] In FIG. 1 a simplified diagram of the ion implantation processcan be seen. The ions are accelerated by application of highelectromagnetic fields, and impact on the surface of the material, beinginserted in the material. This process is carried out withoutoriginating any modification in the surface dimensions of the implantedmaterial, but nevertheless its physico-chemical properties are modified.

[0015] In FIG. 2 detail of an embodiment is shown in which the beam ofions impacts directly on a dental implant, at the same time as thelatter is subjected to a rotational movement. The beam can impact thepiece from different directions, so that it is assured that the wholesurface of the implant is subjected to the ion implantation treatment.

[0016] In FIG. 3 a simplified schematic of a typical process formanufacturing dental implants can be seen.

[0017]FIGS. 4 and 5 show the aspect of a cross-section of the implantslargely surrounded by osseous matter. The samples were prepared havewith Martins and Masson staining, respectively.

[0018]FIGS. 7 and 8 are photographs taken with a sweeping electronicmicroscope, in which the close contact can be observed of the osseousmatter with the surface of the implant which has been subjected to ionimplantation treatment.

[0019]FIGS. 9, 10, 11 and 12 are some photographs taken with a sweepingelectronic microscope which show different details at differentmagnifications of the osseous structure after removal of the treatedimplant.

[0020] In FIG. 13 the XPS spectrum is shown, with the bonding energiesof the elements present in the atomic layers of the bone-implantinterface, of a sample subjected to the ion implantation treatment.

DETAILED DESCRIPTION OF THE INVENTION

[0021] The invention provides a method for the production ofendo-osseous implants or medical prostheses, hereinafter method of theinvention, said endo-osseous implants or medical prostheses beingmanufactured from a base material, by means of a surface ionimplantation treatment of, at least, an element selected among theelements C, O, H, Xe, Ar, He, Kr, Ne and/or a compound which comprisesone or more of said elements, in which an ion beam energy is used ofbetween 1 keV and 1 MeV, in which the process of ion implantation iscarried out in a vacuum chamber with a vacuum better than 10⁻³ millibarsand a dose is applied of, at least, 10¹⁵ ions/cm².

[0022] The term endo-osseous implants or medical prostheses, as it isemployed in this description includes whatever endo-osseous implant orprostheses intended to be in contact with living tissues or cells, orwith corporal or biological fluids.

[0023] As base material use can be made of any metal, metallic alloy,biocompatible material, and mixtures thereof, employed in theelaboration of endo-osseous implants and/or medical prostheses, such asthose materials which satisfy the standard UNE-EN ISO 10993. In aparticular embodiment, said base material is selected among titanium;alloys of titanium, aluminium and vanadium, for example, Ti-6Al-4V;alloys of chromium and cobalt (Cr—Co); alloys of cobalt, chromium andmolybdenum (Co—Cr—Mo), stainless steel, for example, AISI 316 stainlesssteel, etc.

[0024] The method of the invention comprises the implantation of, atleast, an ion of an element selected among the elements C, O, H, Xe, Ar,He, Kr, Ne and/or of an ion of a compound which comprises one or more ofsaid elements, for example, CO, CO_(n), CxHy, etc. (where n is aninteger between 1 and 2, and x and y are integers between 1 and 100.)

[0025] The method of the invention is carried out, advantageously, in atreatment or vacuum chamber with a vacuum level of, at least, 10⁻³millibars.

[0026] Ion implantation, according to the method of the invention, canbe carried out, optionally, in presence of a residual atmosphere in saidvacuum chamber. This residual atmosphere can consist both in thepresence of oxygen and of residual organic compounds, for example,organic compounds produced by the evaporation of an organic compoundduring the process of ion implantation in the treatment chamber. Theimplanted ionic doses can vary within a wide range depending on thenature of the implanted ion, being, in general, greater than 10¹⁵ions/cm² with the object of providing the endo-osseous implant or themedical prostheses with the necessary properties to achieve asignificant enhancement of the osseointegration capacity.

[0027] The process of ion implantation according to the method of theinvention can be carried out over a wide temperature range, for example,it can be carried out at a temperature between −120° C. and 800° C.,preferably, between ambient temperature and 250° C. In a particularembodiment, with the object of favouring mechanisms for diffusion,precipitation or transformation of compounds, the process of ionimplantation according to the method of the invention can be carried outat a temperature of between 250° C. and 800° C. In other applications,these same mechanisms for diffusion, precipitation or transformation canbe achieved by means of heat treatment of the endo-osseous implants orprostheses, when the process of ion implantation has been completed, ata temperature of between 250° C. and 800° C.

[0028] The ion implantation treatment, according to the method of theinvention, can be applied to endo-osseous implants or medical prosthesesby means of techniques of line of sight ion implantation or beam ionimplantation, plasma immersion ion implantation or plasma source ionimplantation, or by means of whatever other equivalent technique.

[0029] As a result of the method of the invention endo-osseous implantsor medical prostheses can be obtained, for example, dental implants,prostheses of hip, knee, etc., with an enhanced degree ofosseointegration thereof, and/or with a reduced degree of lixiviation ofions to the physiological medium in contact with said implants and/orprostheses, and/or with enhanced tribological properties, for example,better resistance to abrasion, decreased friction, etc.

[0030] The endo-osseous implants and prostheses attainable by means ofthe method of the invention constitute an additional object of thisinvention. In a particular embodiment, said endo-osseous implants orprostheses have an enhanced degree of osseointegration, and/or a reduceddegree of ionic lixiviation to the physiologic medium in contact withthe implant or the prostheses, and/or enhanced tribological properties.

[0031] The following example of embodiment illustrates the invention andshould not be taken restrictively with regard to the scope thereof.

EXAMPLE Ion Implantation of CO⁺ Ions in a Dental Implant

[0032] This example illustrates the application of a surface ionimplantation treatment of CO⁺ ions in a dental implant manufactured in atitanium alloy Ti6Al4V. For it, 8 Spline Twist TiTM (Sulzer CalcitekInc.) commercial dental implants were selected, 8 mm long by 3.75 mmdiameter. They are smooth-surface machined screws manufactured inTi6Al4V. For the subsequent tests, other 8 dental implants of the samebatch were reserved without treatment. In FIGS. 4 and 5 the appearanceof these screws can be seen in cross-section.

[0033] The dental implants were cleaned successively in an ultrasonicbath of acetone and ethanol for a minimum period of time of 5 minutes.Subsequently they were all introduced in the vacuum chamber. The vacuumlevel that was reached and maintained during the entire ion implantationprocess was at all times better than 5.10⁻⁷ millibars.

[0034] The ion implantation treatment was carried out in an IonImplanter of the 1090 series by Danfysik AS, located in the facilitiesof Inasmet in Irun. The dental implants were implanted ionically withCO⁺ ions, at an energy of 50 keV with a dose of 5.10¹⁷ ions/cm². Thistreatment was applied to the lateral cylindrical surface and the endsurface of the thread of the dental implants. The temperature of thedental implants did not reach at any time values of more than 170° C.

[0035] In FIG. 1 a simplified schematic of a typical manufacturingprocess of dental implants can be observed.

[0036] According to estimates made with the “Profile Code” softwarepackage, the element implanted under these conditions is in regions ofless than 0.1 μm in depth, atomic concentrations being reached of morethan 25% for both elements in the areas of maximum concentration andnormal incidence of the ion beam.

[0037] The treatment of dental implants by the ion implantationtechnique described above allows the implant failure rate to be reduced,due to an increase in the degree of osseointegration of the dentalimplants in the osseous mass. This has been demonstrated by means ofosseous implantation tests.

Osseous Implantation Test

[0038] Screws of Ti6Al4V with CO⁺ ion implantation have been tested bymeans of the “bone implantation test” according to standard UNE-EN10993-6:1995.

[0039] The objective of this test was to evaluate the biologicalresponse of the osseous tissue to the implanted material. The methodcompares the biological response to implants in test samples with thebiological response to implants in control samples.

Animals

[0040] Rabbits were used, mature male albinos (New Zealand White),animal model with osseous structures of sufficient mass to receive thedental implants, the mean weight of which was 4700 g, with a minimum of4000 g and a maximum of 5200 g. They have been kept and cared foraccording to the ISO 10993-2:1992 standard and in compliance with thelegal regulations of the Ministry of Agriculture, Fishing and FoodstuffsRD 223/1988, Order dated Oct. 13, 1989.

Samples

[0041] 8 smooth-surface machined screws manufactured in Ti6Al4V, 8 mmlong by 3.75 mm diameter, and implanted ionically with CO⁺ according tothe previously described procedure.

Control

[0042] 8 smooth-surface machined screws manufactured in Ti6Al4V, 8 mmlong by 3.75 mm diameter, similar to the samples were used as controlsamples.

Place of Implantation

[0043] 4 screws per rabbit implanted in the tibial plateau.

Operating Procedure

[0044] A general anaesthesia was applied with tiacine hydrochlorate of3.15 mg/500 g intramuscular (i.m.) (ROMPUN 2%®) and ketamine 18 mg/500 gi.m. (KETOLAR 50®), completed with local anaesthesia in the interventionarea with lidocaine 1:100.000, 1 ml in each leg. After shaving anddisinfection of the area, deferred cutaneous incision was carried out,with sterile technique, separation of the fascias and distal inserts ofthe internal straight and semi-tendinous muscles and of the proximalinsert of the cranial tibial muscle and detachment of the periosteum ofthe front face of the proximal epiphysis of both tibias.

[0045] With micromotor and cooling with physiological serum, the osseouscortical mass was drilled at 1500 revolutions/minute, using a ball bit.Next, the implant osseous channel was deepened to 8 mm with bits withexternal cooling of 2 mm in diameter and internal of 3 mm and bit of 3.3mm in diameter, with external irrigation, followed by diestock. Theionically implanted and control dental implants were placed in thechannel by manual insertion employing a ratchet key. The wound wasclosed by planes with polyglactin suture 4/0 (Vycril®) and the skin withsilk 3/0 (Aragó®).

[0046] Antibiotic prevention was administered with benzylpenicillinbenzathine 50×10³ U/kg/week i.m. (BENZETACIL 1.200.000®). Locally, aftershaving the paws at the level of the tibial plateaux, iodized povidone(Betadine®) was applied on the area. During the following days analgesictreatment was administered with acetil salicylate of lysine 10 mg/500 g,i.m. (INYESPRIN®). In the days following, the areas of the surgicalwounds were cleaned and 0.12% chlorhexidine and antibiotic ointment(Furacin®) was applied locally.

[0047] The animals remained for three months housed individually in acontrolled medium with light/darkness cycles (12 h), air conditioning(15 renovations/h) and at a temperature controlled between 18° C. and22° C., complying with the legal regulations in this respect.

[0048] After sedation with diazepam 5 mg/kg i.m. (Valium®), the animalswere sacrificed using a carbon monoxide chamber, the tibial plateauxcontaining the implants were extracted in block and introduced in 4%formol for later processing thereof.

[0049] The osseous blocks, containing the implants, were subjected to atechnique of desiccation and dehydration in 60%, 80%, 96% and 100%acetones and alcohols, concluding in 100% xylol. Later separation,cutting and fine polishing were carried out according to the DONATHtechnique, for obtaining histological sections. To make microscopicstudy possible, the samples were subjected to staining. An example ofthe appearance of these samples can be seen in FIGS. 4 and 5.

Appraisal of Results

[0050] 1. Histological Evaluation

[0051] The evaluation of the histological preparations was done by meansof prior capture of images with a digital macrophotography system(Nikon). The images so obtained were analysed by means of an Omnimetimage analyser, and processed with an image handling program AdobePhotoshop 5.0.

[0052] When defining the osseointegrated area the following criteriawere adopted:

[0053] The area in contact with spongy or trabecular bone was notconsidered osseointegrated, only that with cortical bone.

[0054] The adjacent areas were considered osseointegrated which forcontour similarity with the cortical bone could be assumed to have beendisplaced in the preparation process.

[0055] Those areas were considered osseointegrated which, in a computeramplification of the area (×200) showed small and fine layers ofcortical osseous tissue adhered to the implant.

[0056] Considered as osseointegrated as a single area were thoseadjacent integrated areas, the separation distance of which was lessthan one quarter of the width of the thread of the implant.

[0057] The results showed statistically significant differences betweenthe implants located on the tibia of the rabbit in the epiphyseal area(distal) or metaphyseal area (mesial), osseointegration being moredifficult in the first case, as it concerns an area poorer in corticalbone. In this last case, a significantly greater bone-implant union wasappreciated in the case of implants with ion implantation treatment, ascan be observed in FIG. 6.

[0058] 2. Study by Means of Electronic Microscopy

[0059] The type of union was analysed between the bone and the implant.In FIGS. 7 and 8 a close contact can be observed between bone andimplant at different magnifications. The whiter images correspond tobone and the darker to soft tissue. This was checked by a compositionanalysis by electron microprobe (EDS) of both areas.

[0060] Also, in one of the samples the implant of the histologicalsection was removed and the bone observed from the cavity of theimplant. The images allow the osseous structure in contact with theimplant to be seen clearly (see FIGS. 9, 10, 11 and 12).

[0061] 3. Study by Means of XPS

[0062] By means of this technique the composition of the elementspresent in the atomic layers of the bone-implant interface was analysed,and the type of linkage between the titanium and the osseous tissue towhich it is joined (FIG. 13).

[0063] It was observed that maximum energy was at a binding energycorresponding to a Ti—O—C bond, where the carbon belonged to a complexorganic molecule. Said Ti—O—C bond present in the interface of thesurface of the implant corresponds to the protein-metallic oxide unionformed during the period of permanency in the living animal.

Conclusion

[0064] Surface ion implantation treatment with CO⁺, induces changes inphysical structure and surface electrochemistry, increasing adhesion tothe surrounding biological tissue.

[0065] The histomorphometric results obtained confirm the improvement inosseointegration, in terms of bone implant contact.

[0066] Additionally, ionic implantation improves tribologicalproperties, increasing the resistance of the material treated to wearand abrasion, it increases resistance to corrosion and chemical attack,reducing the possibility of electrochemical reaction with the medium,therefore diminishing lixiviation of the material.

1. A method for the production of endo-osseous implants or medicalprostheses, said endo-osseous implants or medical prostheses beingmanufactured from a base material, by means of a surface ionimplantation treatment of, at least, an element selected among theelements C, O, H, Xe, Ar, He, Kr, Ne and/or a compound which comprisesone or more of said elements, in which an ion beam energy is employed ofbetween 1 keV and 1 MeV, in which the process of ion implantation iscarried out in a treatment chamber with a vacuum better than 10⁻³millibars and a dose is applied of, at least, 10¹⁵ ions/cm².
 2. Methodaccording to claim 1, in which said base material is selected among ametal, a metallic alloy, a biocompatible material, and mixtures thereof,employed in the elaboration of endo-osseous implants and/or medicalprostheses which comply with the standard UNE-EN ISO
 10993. 3. Methodaccording to any one of the previous claims, in which the process of ionimplantation takes place in presence of a residual atmosphere of oxygenor of organic compounds in the treatment chamber.
 4. Method according toany one of the previous claims, in which an organic compound isevaporated during the process of ion implantation in the treatmentchamber.
 5. Method according to any one of the previous claims, in whichthe process of ion implantation is applied on said endo-osseous implantsor medical prostheses by means of techniques of line of sight ionimplantation or beam ion implantation, plasma immersion ion implantationor plasma source ion implantation, or equivalent techniques.
 6. Methodaccording to any one of the previous claims, in which the process of ionimplantation is carried out at a temperature between −120° C. and 800°C.
 7. Method according to any one of the previous claims, in which theendo-osseous implants or the prostheses undergo a thermal treatment at atemperature of between approximately 250° C. and 800° C. after theprocess of ion implantation.
 8. An endo-osseous implant or medicalprostheses obtainable by means of the method of whatever of the previousclaims.
 9. Endo-osseous implant or medical prostheses according to claim8, in which said implant or prostheses has an enhanced degree ofosseointegration, and/or a reduced degree of ionic lixiviation to thephysiologic medium in contact with the implant or the prostheses, and/orimproved tribological properties.